Clinical Translational Core Project Summary Major advances in our understanding of the genetic and environmental structure of neurodevelopmental disorders present new opportunities to prevent or ameliorate intellectual and developmental disabilities (IDD). The Clinical Translational Core (CTC) of the IDDRC@WUSTL will function as a conduit from new discovery in pathogenic mechanisms to clinical innovation, as well as the reverse (i.e., from clinical data acquisition to breakthroughs that deepen our understanding of complex disease mechanisms). Both directions are crucial and fundamentally interact to facilitate the development of higher-impact interventions for IDD, which is the overarching goal of the Center. The Core will catalyze this bidirectional exchange and serve as an integrative scientific hub of the IDDRC@WUSTL. The specific aims of the CTC are as follows: (1) To provide investigators with the expertise, resources, and assessment services needed to complete comprehensive behavioral and genomic characterizations of human subjects. Behavioral and genomic characterization will occur via a CTC unit structure that features a Human Behavioral Assessment Unit (HBAU) and a Human Genomic Characterization Unit (HGCU). The HBAU is a unique, multifaceted behavioral assessment program that provides state-of-the-art phenotyping relevant to the characterization of developmental, behavioral, and environmental aspect features of infants and children affected by or at risk for IDD. The HGCU was established during Year 05 of the IDDRC@WUSTL and has already garnered some $300,000 of supplemental institutional and philanthropic support, leveraging world-class facilities of WUSTL for genomic research, including the Genome Technology Access Center (GTAC) for genomic sequencing and the Genomic Engineering and iPSC Center (GEiC) of the CTSA for modeling inherited disease mechanisms. HGCU team members include international authorities in neurogenetics, clinical genetics, and human genetics (including deep expertise in the interpretation of deleteriousness of disease-causing variants). (2) to strategically harness services and expertise of allied WUSTL facilities that critically and cost-effectively complement the IDDRC@WUSTL scientific cores to constitute a discovery pipeline for higher-impact intervention for individuals affected by or at risk for IDD. (3) To support the bidirectional translational interface between the discovery of pathogenic mechanisms and the development of novel approaches to IDD prevention and treatment for patients.